NK Cell Infusion for Patients With Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

Clinical Study of Natural Killer Cell Infusion in Patients With Acute Myeloid Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04221971
• Other study ID #: 2019PHD005-01
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: October 2020
• Est. completion date: April 2022

Study information

• Verified date: September 2020
• Source: Peking University People's Hospital
• Contact: Xiang-Yu Zhao, M.D.
• Phone: 8610-88325949
• Email: zhao_xy[@]bjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Natural killer (NK) cells exert antitumor effects via their cytotoxic and cytokine-secreting capacity without present of clinical symptoms. In recent years, with the continuous advancement of in vitro expansion methods, the application of good quality management technology, NK cells could be clinical grade expanded without the need for pre-purification, feeder-free, and serum-free culture. In this clinical trial the investigators want to demonstrate the safety and efficacy chemotherapy combined with donor-derived in vitro activated NK cells infusion for high risk AML patients.

Description:

Despite improvements in new drugs and allogeneic stem cell transplantation (allo-SCT), relapse remains a problem for patients with acute myeloid leukemia (AML). Natural killer (NK) cells exert antitumor effects via their cytotoxic and cytokine-secreting capacity without present of clinical symptoms.

In recent years, with the continuous advancement of in vitro expansion methods, the application of good quality management technology (GMP technology), NK cells could be clinical grade expanded without the need for pre-purification, feeder-free, and serum-free culture. Preclinical studies have confirmed that adoptive infusion expanded and activated NK cells can specifically recognize and kill tumor cells in mice without causing GVHD, which is a safe and effective treatment.

Therefore, in this clinical trial the investigators want to enroll patients with acute AML (excluding APL) who are continued to be unresolved, or relapsed after remission, or continued to be MRD-positive after induction and consolidation according to NCCN standard chemotherapy regimen. Chemotherapy was combined with donor-derived in vitro activated NK cells infusion to evaluate the safety and effectiveness effect of NK cells and to explore the dynamics of NK in vivo after adoptive infusion.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: April 2022
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. AML patients receiving standard NCCN induction and consolidation chemotherapy;

2. Age> = 18 years old;

3. Relapsed and refractory AML: continued non-remission after induction and consolidation chemotherapy with NCCN standard protocol, or relapse after remission, or continued MRD positive;

4. MDS-RAEB, MDS-AML, MPD-AML;

5. ECOG=3;

6. No serious organ dysfunction within 2 weeks before treatment:

1. Heart: no arrhythmia and LVEF=50% and no pericardial effusion;

2. Liver: liver function <2 times the upper limit of ALT and <1.5 times the upper limit of total bilirubin, no active hepatitis;

3. Kidney: serum creatinine <1.5 mg / dl; or if serum creatinine exceeds the upper limit, serum creatinine clearance should be CrCl> 50 ml / min;

4. indoor fingertip blood oxygen saturation ? 92%;

7. Expected survival time = 3 months;

8. The interval between re-induction therapy and NK cell therapy is at least 2 weeks, and the toxic and side effects of all induction remission treatments have disappeared; if the patient is receiving non-invasive chemotherapy, such as hydroxyurea, low-dose cytarabine, before receiving this program Should be discontinued before;

9. All patients and donors are willing to join this clinical trial and sign informed consent.

Exclusion Criteria:

1. Combined with a history of other malignant tumors <5 years (except cured skin basal cell carcinoma, cured cervical carcinoma in situ and gastrointestinal tumors confirmed to be cured by endoscopic mucosal resection);

2. Have received bone marrow or organ transplant;

3. Those who are allergic to the biological agents used in this treatment;

4. active infection;

5. Those who received other cell treatments such as DLI, CMV-CTL, EBV-CTL;

6. HBV carriers;

7. Patients with extramedullary recurrence;

8. Chest radiographic examination to determine patients with pulmonary inflammation;

9. Researchers do not consider it appropriate to participate in this trial.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• chemotherapy combined with NK cells infusion
chemotherapy combined with NK cells infusion

Locations

Country	Name	City	State
China	Peking University Institute of Hematology	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking University People's Hospital	The University of Science and Technology of China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Closely monitor the patient's temperature, rash, BP, and other adverse reactions during the 48 hours after the infusion, and pay attention to acute and chronic GVHD; follow up once every 1-2 weeks within 6 months after the infusion, and review the blood count and biochemistry. Increase or decrease the relevant inspections and inspection frequencies as appropriate according to the condition;	Two months after NK treatment
Secondary	Number of participants acheived CR post NK treatment	To evaluate the CR rate 1 month after NK treatment	One month after NK treatment
Secondary	Monitor the metabolism, migration and reconstruction of NK cells in vivo post NK treatment	The number of NK cells were evaluated before and after the completion of the infusion.	One month after NK treatment
Secondary	Assess the cell count recovery time of peripheral blood in chemotherapy combined with NK infusion	The blood count were evaluated closely before and after the completion of the infusion.	Two months after NK treatment
Secondary	Number of participants relapsed post NK treatment	To evaluate the bone marrow status every months after NK treatment	Every months after NK treatment within 1 year